UK patent No. GB 2,225,321 discloses enantiomers of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid dihydrochloride, known as a non-sedative antihistamine drug under the generic name of cetirizine. Cetirizine is represented by the following structure:

Processes for the preparation of cetirizine and related compounds were disclosed in the UK patent No. GB 2,225,321, U.S. Pat. No. 5,478,941 and PCT patent publication No. WO 2006/094648 A1.
In the preparation of substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine, substantially optically pure levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenylmethyl]piperazine of formula I:
is a key intermediate. According to the UK patent No. GB 2,225,321, the enantiomers of 1-[(4-chlorophenyl)phenylmethyl)piperazine are obtained by chemical resolution of the racemic form, using conventional methods, in particular, by salt formation with a suitable selected optical isomer of tartaric acid.
The major disadvantages of the process are on one hand, that the yield of the resolution step of the racemic 1-[(4-chlorophenyl)phenylmethyl]piperazine is extremely low and, on the other hand, that the optical purity of the dextrorotatory and levorotatory enantiomers so obtained is insufficient and does not allow the final product to be prepared with an optical purity greater than 95%.
The U.S. Pat. No. 5,478,941 disclosed process for preparing levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenyl methyl]-4-[(4-methylphenyl)sulfonyl]piperazine and also preparation of the substantially optically pure enantiomers of 1-[(4-chlorophenyl)phenylmethyl]piperazine using enantiomers of 1-[(4-chlorophenyl)phenylmethyl]-4-[(4-methyl phenyl)sulfonyl]piperazine.
The PCT patent publication No. WO 2006/094648 A1 disclosed the preparation of levocetirizine using the resolution of racemic 2-[4-[4-chlorobenzhydryl]piperazin-1-yl]ethoxyacetamide with (S)-pyrrolidine-5-carboxylic acid and followed by hydrolysis.
Since resolution is performed at an advanced intermediate, there in a loss of costly intermediates and so, the process is commercially not viable.
However, a need still remains for an improved and commercially viable process of preparing substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine, and their pharmaceutical acceptable acid addition salts thereof, that will solve the aforesaid problems associated with processes described in the prior art and will be suitable for large scale preparation, in terms of simplicity, purity and yield of the product.
One object of the present invention is to provide a novel process for preparation of substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine intermediate, 1-[(4-chlorophenyl)phenylmethyl]piperazine.
Another object of the present invention is to provide a process for preparing substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine and their pharmaceutical acceptable acid addition salts thereof in high purity and in high yield using novel intermediates.
Another object of the present invention is to provide a novel intermediates for the preparation of substantially optically pure levorotatory and dextrorotatory enantiomers of 1-[(4-chlorophenyl)phenylmethyl]piperazine.